The ‘obesity paradox’ in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial

Background

BMI is an established risk factor for the development of atrial fibrillation (AF) and an independent predictor of progression from paroxysmal to sustained forms of AF [1,2]. However, the prognostic impact of obesity on clinical outcomes among patients with AF is unclear, since there are data showing that an overweight status and obesity may be associated with a favourable prognosis in patients with CVD [3,4].
This ‘obesity paradox’ has not been studied thoroughly in AF patients, but data show that:

overweight status and obesity were associated with a lower risk of death from any cause or CV mortality compared with normal weight [5,6].

overweight status and obesity were associated with a higher risk of a composite endpoint (ischemic stroke, thromboembolism, or death) after adjustment [8].

there was no association between obesity and risk of thromboembolic events [9].

In this study, the association between various measures of adiposity [BMI and waist circumference (WC)] and clinical outcomes was evaluated in 18,107 participants randomised to apixaban or warfarin in the ARISTOTLE trial. The clinical outcomes included stroke or systemic embolism (SE), a composite endpoint (stroke, SE, myocardial infarction, or all-cause mortality), all-cause mortality, and major bleeding.

Main results

In multivariable analyses, compared with normal BMI, a higher BMI was associated with:

Patients treated with apixaban had lower rates of both the efficacy and safety outcomes across all categories of BMI compared with patients treated with warfarin

There was a statistically significant interaction (P-interaction = 0.01) between BMI and the effects of apixaban compared with warfarin concerning major bleeding, with a larger reduction in bleeding with normal vs. higher BMI

Conclusion

Prospective data showed that in patients with AF treated with oral anticoagulants, higher BMI and WC are associated with a more favourable prognosis. Adiposity, as measured by BMI or WC did not affect the efficacy of apixaban in these anticoagulated patients, but the reduction obtained with apixaban in major bleeding may be reduced at higher vs. normal BMI.